# Effectiveness of Indapamide Prolonged‐Release and Perindopril Versus Perindopril Monotherapy for Treated Uncontrolled Hypertension: A Target Trial Emulation

## TL;DR

Adding indapamide to perindopril lowers blood pressure more effectively than using perindopril alone in patients with uncontrolled hypertension.

## Contribution

This study uses real-world data to emulate a clinical trial and demonstrates the added benefit of combining indapamide with perindopril for hypertension.

## Key findings

- Adding indapamide to perindopril reduced systolic blood pressure by an average of 6.3 mmHg after 8 weeks.
- Sensitivity analyses confirmed the robustness of the results despite different assumptions.
- The combination therapy showed clinically meaningful improvements over monotherapy.

## Abstract

To assess the effectiveness of indapamide prolonged release and perindopril in combination using blood pressure (BP) records collected in routine practice.

Using a target trial emulation framework, an observational retrospective cohort study was conducted. The data source was the United Kingdom's CPRD Aurum general practice database. Adults with systolic BP (SBP) ≥ 145 mmHg treated with perindopril 4/5 mg for ≥ 4 weeks at a stable dose who either added indapamide 1.5 mg to perindopril (n = 193) or continued on perindopril monotherapy (n = 14 571) were included. Balance between treatment arms was achieved with propensity score matching; results were explored in additional analyses using different eligibility criteria and alternative statistical methodologies. The primary outcome was change in SBP from baseline to Week 8 between indapamide added to perindopril versus perindopril monotherapy.

In the primary analysis, indapamide added to perindopril yielded an additional SBP reduction of −6.3 mmHg (95% confidence interval [CI] −8.7 to −3.9) over perindopril monotherapy at Week 8. Results of additional analyses were consistent with the main analysis, but effect estimates varied due to diverse underlying assumptions.

Target trial emulation allowed assessment of antihypertensive treatment effectiveness, and indapamide plus perindopril yielded clinically meaningful decreases in SBP over perindopril monotherapy. Secondary and sensitivity analyses support that these findings were robust.

Adults with a systolic blood pressure ≥ 145 mmHg after at least 4 weeks of treatment with perindopril 4/5 mg per day who added treatment with indapamide 1.5 mg presented a reduction in systolic blood pressure of −6.3 mmHg on average (95% confidence interval, −8.7 to −3.9) over perindopril monotherapy after 8 weeks of treatment.Sensitivity analyses that challenged the assumptions made to implement this analysis in the United Kingdom's CPRD Aurum general practice database yielded consistent results.

Adults with a systolic blood pressure ≥ 145 mmHg after at least 4 weeks of treatment with perindopril 4/5 mg per day who added treatment with indapamide 1.5 mg presented a reduction in systolic blood pressure of −6.3 mmHg on average (95% confidence interval, −8.7 to −3.9) over perindopril monotherapy after 8 weeks of treatment.

Sensitivity analyses that challenged the assumptions made to implement this analysis in the United Kingdom's CPRD Aurum general practice database yielded consistent results.

Treatment of increased blood pressure (hypertension) relies primarily on oral antihypertensive medication. When hypertension it is not well controlled with a single drug, medications with different mode of action can be combined. In this study data coming from routinely collected medical information in the UK was used to study the effect of adding indapamide (1.5 mg) to perindopril (4/5 mg) in patients whose hypertension was not well controlled with perindopril alone. The results are highly compatible with a decrease in blood pressure from −8.7 to −3.9 mmHg after 8 weeks of treatment.